Background: Ischemic heart disease (IHD) disease represents a major source of morbidity and mortality among veterans. Optimal management of IHD requires the use of medications, including statins, beta- blockers, and platelet inhibitors, to prevent serious cardiovascular event (CVE), such as myocardial infarctions. Unfortunately, non-adherence to these medications is common and results from a complex series of factors. Studies have found that for veterans with IHD, the most frequent causes of missed doses are forgetfulness and carelessness, a situation exacerbated by a health care system that: 1) only passively monitors adherence; 2) addresses instances of non-adherence long after they have occurred; 3) attempts to manage adherence barriers in an non-systematic, inefficient patient-by-patient manner, rather than through population health management using a systematic approach. Prior attempts to correct this problem have frequently employed non-targeted, non-real-time, un-tailored interventions, with disappointing results. Proposal: In concert with input from our VA operational partners, this proposal capitalizes on the infrastructure of the national VA Clinical Assessment, Reporting, and Tracking System (CART) Program. CART will identify and monitor veterans with IHD following percutaneous coronary intervention (PCI)-a cardiac procedure commonly used among IHD patients. Collecting extensive data at over 60 Cardiac Catheterization Laboratories (CCLs) for over 13,000 PCI's annually across the U.S., CART is uniquely suited for the proposed work. Our overall hypothesis posits that a multi-faceted, targeted, patient-centered medication adherence intervention will improve adherence rates for statins, beta-blockers, and platelet inhibitors and thus, the cardiac health of veterans with IHD. Methods: The intervention will be tested using a novel, modified stepped-wedge study design. Known as VA SEPPRMACI (Secondary Event Prevention using Population Risk Management After PCI), this intervention will consist of: proactive real-time adherence monitoring of patients and targeting of individuals only when they have exhibited non-adherence behavior (i.e., if patients have not refilled their medication more than 4 days after a platelet inhibitor was due to be refilled and 7 days after a statin or beta-blocker was due). The intervention will employ a tailored, escalating-intensity approach which begins with a combination of a personalized short messaging service (SMS) text messages and/or interactive voice response (IVR) telephone technology (depending on patient preference). Patients failing these components by not refilling their medication escalate to a trained research interventionalist. The interventionalist will contact the patient and address the complex adherence barriers specific to each patient using a structured, systematic approach. We will test the intervention at 4 CCLs and have 12 sites serve as usual care controls. This novel approach provides greater statistical power by supplementing the pre-intervention/usual care observation periods with concurrent usual care observation periods from the 12 additional CCLs. Endpoints established by our operational partners consist of both intermediate and hard clinical outcomes. Specifically, we will assess the effect of the intervention on a measure adherence (proportion of days covered, Aim 1, primary end point) and on CVEs during 12 months of follow-up (Aim 2, exploratory/secondary end point). We will also establish the cost to implement and maintain the intervention, above the cost of usual care, and the incremental cost effectiveness of the intervention (Aim 3).